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Recent clinical advances with camptothecin analogues

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Concepts, Mechanisms, and New Targets for Chemotherapy

Part of the book series: Cancer Treatment and Research ((CTAR,volume 78))

Abstract

In the 1950s, Monroe Wall and his colleagues isolated a compound with antileukemia activity from the bark of the tree Camptotheca acuminata [1]. The compound, camptothecin, demonstrated encouraging activity in early clinical testing but was abandoned due to unpredictable toxicity. In 1985, Hsaing and Liu observed that the cytotoxic effect of camptothecin requires the nuclear enzyme topoisomerase I [2]. This finding coincided with the development of the semisynthetic camptothecin analogues topotecan, irinotecan, and 9-aminocamptothecin (see figure 2-1). Collectively, these important observations have ushered in a period of intense investigative interest in this class of drugs. The availability of a series of new agents with a unique mechanism of action and promising preclinical activity has stimulated tremendous excitement about these agents. The remainder of this chapter reviews the mechanism of action, clinical pharmacology, toxicity profiles, and antitumor activities of these drugs used either as single agents or in combination chemotherapy.

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Authors
  1. William J. Slichenmyer
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  2. Ross C. Donehower
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  1. University of Southern California Cancer Center, USA

    F. M. Muggia

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Slichenmyer, W.J., Donehower, R.C. (1995). Recent clinical advances with camptothecin analogues. In: Muggia, F.M. (eds) Concepts, Mechanisms, and New Targets for Chemotherapy. Cancer Treatment and Research, vol 78. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2007-8_2

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